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  • Williford Cates posted an update 3 weeks, 2 days ago

    Most of these dysregulated metabolites are tightly related to energy and phospholipid metabolism. This study revealed a deep metabolic remodelling in phospholipids and energy metabolism in DMD. This systems-based approach enabled exploring the metabolism in DMD in an unprecedented holistic and unbiased manner with hypothesis-free strategies.Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.Silicon (Si), as a quasi-essential element, has a vital role in alleviating the damaging effects of various environmental stresses on plants. Cadmium (Cd) stress is severe abiotic stress, especially in acidic ecological conditions, and Si can demolish the toxicity induced by Cd as well as acidic pH on plants. Based on these hypotheses, we demonstrated 2-repeated experiments to unfold the effects of Si as silica gel on the root morphology and physiology of wheat seedling under Cd as well as acidic stresses. For this purpose, we used nine treatments with three levels of Si nanoparticles (0, 1, and 3 mmol L-1) derived from sodium silicate (Na2SiO3) against three concentrations of Cd (0, 50, and 200 µmol L-1) in the form of cadmium chloride (CdCl2) with three replications were arranged in a complete randomized design. The pH of the nutrient solution was adjusted at 5. The averages of three random replications showed that the mutual impacts of Si and Cd in acidic pH on wheat roots depend on the concentrations of Si and Cd. The collective or particular influence of low or high levels of Si (1 or 3 mM) and acidic pH (5) improved the development of wheat roots, and the collective influence was more significant than that of a single parallel treatment. The combined effects of low or high concentrations of Cd (50 or 200 µM) and acidic pH significantly reduced root growth and biomass while increased antioxidants, and reactive oxygen species (ROS) contents. The incorporation of Si (1 or 3 mmol L-1) in Cd-contaminated acidic nutrient solution promoted the wheat root growth, decreased ROS contents, and further increased the antioxidants in the wheat roots compared with Cd single treatments in acidic pH. The demolishing effects were better with a high level of Si (3 mM) than the low level of Si (1 Mm). In conclusion, we could suggest Si as an effective beneficial nutrient that could participate actively in several morphological and physiological activities of roots in wheat plants grown under Cd and acidic pH stresses.The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases.Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain unknown. In this work we studied the broad molecular changes involved in the induction of MHE with the goal of identifying (1) altered genes and pathways in peripheral blood cells associated to the appearance of MHE, (2) serum metabolites and cytokines with modified levels in MHE patients and (3) MHE-regulated immune response processes related to changes in specific serum molecules. We adopted a multi-omic approach to profile the transcriptome, metabolome and a panel of cytokines of blood samples taken from cirrhotic patients with or without MHE. Transcriptomic analysis supports the hypothesis of alternations in the Th1/Th2 and Th17 lymphocytes cell populations as major drivers of MHE. Cluster analysis of serum molecules resulted in six groups of chemically similar compounds, suggesting that functional modules operate during the induction of MHE. Finally, the multi-omic integrative analysis suggested a relationship between cytokines CCL20, CX3CL1, CXCL13, IL-15, IL-22 and IL-6 with alteration in chemotaxis, as well as a link between long-chain unsaturated phospholipids and the increased fatty acid transport and prostaglandin production. We found altered immune pathways that may collectively contribute to the mild cognitive impairment phenotype in MHE. Our approach is able to combine extracellular and intracellular information, opening new insights to the understanding of the disease.The feeding behavior of the giant ambush-predator “Bobbit worm” (Eunice aphroditois) is spectacular. They hide in their burrows until they explode upwards grabbing unsuspecting prey with a snap of their powerful jaws. The still living prey are then pulled into the sediment for consumption. Although predatory polychaetes have existed since the early Paleozoic, their bodies comprise mainly soft tissue, resulting in a very incomplete fossil record, and virtually nothing is known about their burrows and behavior beneath the seafloor. Here we use morphological, sedimentological, and geochemical data from Miocene strata in northeast Taiwan to erect a new ichnogenus, Pennichnus. This trace fossil consists of an up to 2 m long, 2-3 cm in diameter, L-shaped burrow with distinct feather-like structures around the upper shaft. A comparison of Pennichnus to biological analogs strongly suggests that this new ichnogenus is associated with ambush-predatory worms that lived about 20 million years ago.Mobile devices are increasingly permeating healthcare and are being regularly used by healthcare providers. We examined the prevalence and frequency of mobile device use, and perceptions around clinical and personal usage, among healthcare providers (attending physicians, residents, and nurses) in the Emergency Department (ED) of a large academic medical center in Lebanon. MMP-9-IN-1 purchase Half of the target population (N = 236) completed the cross-sectional electronic questionnaire. Mobile device usage for personal matters was uniform across all providers, with the highest usage reported by medical students (81.3%) and lowest by attendings (75.0%). Medical formulary/drug referencing applications were the most common application used by providers followed by disease diagnosis/management applications, 84.4% and 69.5% respectively. Most respondents agreed that mobile devices enabled better-coordinated care among providers and were beneficial to patient care. Most respondents also agreed that mobile device use assisted in quickly resolving personal issues and reduced their feeling of stress, yet the majority did not feel that personal usage improved performance at work. Study findings revealed that although healthcare providers value mobile devices’ positive impact on coordination of care, the reverse spillover effect of personal issues into the workplace enabled by mobile devices might have some negative impact on performance of staff at work.Ticks are significant nuisance pests and vectors of pathogens for humans, companion animals, and livestock. Limited information on tick feeding behaviors hampers development and rigorous evaluation of tick and tick-borne pathogen control measures. To address this obstacle, the present study examined the utility of AC-DC electropenetrography (EPG) to monitor feeding behaviors of adult Dermacentor variabilis and Amblyomma americanum in real-time. EPG recording was performed during early stages of slow-phase tick feeding using an awake calf host. Both tick species exhibited discernable and stereotypical waveforms of low-, medium-, and high-frequencies. Similar waveform families and types were observed for both tick species; however, species-specific waveform structural differences were also observed. Tick waveforms were hierarchically categorized into three families containing seven types. Some waveform types were conserved by both species (e.g., Types 1b, 1c, 2b, 2c) while others were variably performed among species and individually recorded ticks (e.g., Types 1a, 2a, 2d). This study provides a proof-of-principle demonstration of the feasibility for using EPG to monitor, evaluate, and compare tick feeding behaviors, providing a foundation for future studies aimed at correlating specific feeding behaviors with waveforms, and ultimately the influence of control measures and pathogens on tick feeding behaviors.The magnetic properties of [Formula see text], a paradigmatic hexaferrite for permanent magnet applications, have been addressed in detail combining density functional theory including spin-orbit coupling and a Hubbard U term with Monte Carlo simulations. This multiscale approach allows to estimate the Néel temperature of the material from ab initio exchange constants, and to determine the influence of different computational conditions on the magnetic properties by direct comparison versus available experimental data. It is found that the dominant influence arises from the choice of the Hubbard U term, with a value in the 2-3 eV range as the most adequate to quantitatively reproduce the two most relevant magnetic properties of this material, namely its large perpendicular magnetocrystalline anisotropy and its elevated Néel temperature.